Broad T Cell Immunity to the LcrV Virulence Protein is Induced by Targeted Delivery to DEC-205/CD205-Positive Mouse Dendritic Cells
Abstract
There is a need for a more efficient vaccine against the bacterium Yersinia pestis, the agent of pneumonic plague. The F1-LcrV (F1-V) subunit vaccine in alhydrogel is known to induce humoral immunity. In this study, we utilized DC to investigate cellular immunity. We genetically engineered the LcrV virulence protein into the anti-DEC-205 CD205 mAb and thereby targeted the conjugated protein directly to mouse DEC205+ DC in situ. We observed antigen-specific CD4+ T cell immunity measured by intracellular staining for IFN-gamma in three different mouse strains (C57BL/6, BALB/c, and C3F/HeJ), while we could not observe such T cell respinses with F1-V vaccine in alhydrogel. Using a peptide library for LcrV protein, we identified two or more distinct CD4+ T cell mimetopes in each MHC haplotyupe, consistent with the induction of broad immunity. When compared to nontargeted standard protein vaccine, DC targeting greatly the efficiency for inducing IFN-gamma-producing T cells. The targeted LcrV protein induced antibody responses to a similar extent as the F1-V subunit vaccine, but Th1-dependent IgG2a and IgG2c isotypes were observed only after anti-DEC-205:LcrV mAb immunization. This study sets the stage for the analysis of functional roles of IFN-gamma-producing T cells in Y. pestis infection.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 13, 2007
- Accession Number
- ADA476395
Entities
People
- Bradford S. Powell
- Chae Gyu Park
- Haekyung Lee
- Ralph M. Steinman
- Rebecca M. Lynch
- Sung Ho Park
- Yoonkyung Do
- Young-sun Kang
Organizations
- The Rockefeller University